Introduction: Steatosis is the leading reason for donor livers discarding and contributes significantly to the worsening shortage of organs for transplantation. Steatotic livers commonly fail to recover function during ex-vivo normothermic machine perfusion (NMP). Whether extra-corporeal delivery of therapeutic agents could rescue more steatotic organs is not yet known. We aimed to assess the effect of a defatting cocktail tested in-vitro, using primary human hepatocytes, on lipid metabolism and viability recovery of steatotic donor livers during NMP.

Methods: Six human livers designated histologically macrosteatotic were perfused using NMP for up to 24 hours after cold storage. They were randomly allocated to an intervention group in which the perfusate was supplemented with the combination of drugs and a control group that received only the vehicle (dimethyl sulfoxide [DMSO]<0.1%). Viability based on lactate clearance criteria was assessed at 4 hours. Tissue biopsies, perfusate and bile were sampled and measurements compared using non-parametric tests.

Results: Donor baseline donor demographics were comparable between the groups. The median cold ischemia time was 11:51 (interquartile range 10:10-12:53) hours that was similar in both groups (p>0.99). Treatment with the cocktail resulted in a 3-fold increase in the total cholesterol in the perfusate (p=0.043) and 2.5-fold increase in triglycerides (p=0.044) compared with control livers over 12 hours. Histology showed a reduction of 18% in large droplet macrovesicular steatosis (p=0.020) over 12 hours in the treated group. Bile production was also improved in the treated group at 12-hour (35 ml [35-48] vs. 4 ml [2-15], p=0.048). All livers (3/3) in the treatment group reached viability compared with one (1/3) in the control group (p=0.051).

Conclusion: This is the first study in steatotic human livers to show that pharmacological defatting is feasible and it can enhance lipid metabolism, bile production and improve the rescue of steatotic livers.

CITATION INFORMATION: Boteon Y., Attard J., Laing R., Boteon A., Bhogal R., Reynold G., Neil D., Mergental H., Mirza D., Afford S. Pharmacological Defatting of Steatotic Human Livers Using a Novel Perfusion Solution during Normothermic Machine Perfusion Am J Transplant. 2017;17 (suppl 3).

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